The selective and high-yielding preparation of sugars by chemical methodology represents an ongoing challenge in organic synthesis. The usefulness of sugars, particularly oligosaccharides, is unquestioned, among whose applications are vaccines, antibiotics, molecular recognition, and other medical therapy. Chemical glycosylation reactions enable the coupling reaction of a glycosyl donor to a glycosyl acceptor to form an (oftentimes non-naturally occurring) glycoside. If both the donor and acceptor are sugars, then the product is an oligosaccharide. The reaction requires activation with a suitable activating reagent. The reactions often result in a mixture of products due to the creation of a new stereogenic center at the anomeric position of the glycosyl donor. The formation of a glycosidic linkage allows for the synthesis of complex polysaccharides which may play important roles in biological processes and pathogenesis and therefore having synthetic analogs of these molecules allows researchers to answer persistent questions in diverse scientific disciplines.
A glycosyl donor is a sugar with a suitable leaving group at the anomeric position. This group undergoes activation under the reaction conditions and is eliminated or displaced either before or after the formation of a new chemical bond between donor and acceptor. The leaving group is typically a halogen, thioether, or trichloroacetimidate.
A glycosyl acceptor is any group capable of forming a bond with the anomeric carbon atom of the glycosyl donor. Oftentimes it is a sugar with an unprotected nucleophilic hydroxyl group which may attack the anomeric carbon of the oxocarbenium ion formed during the reaction and allow for the formation of the glycosidic bond.
An activator is commonly a Lewis acid which enables the leaving group at the anomeric position to leave and results in the formation of the oxocarbenium ion.
In practice, glycosylation reactions are limited in terms of substrate scope, yield, and selectivity. Therefore, a tremendous need exists for new glycosylation methods that overcome ongoing problems in this research area, including new activation agents and leaving groups.